We propose to develop a Center for Systems Biology to promote interdisciplinary scientific investigation and education in Chicago. Faculty in the Institute for Genomics and Systems Biology at the University of Chicago will take a leadership role and together with collaborators at other Chicago institutions will create a broad outreach to the community. The Centers scientific program will focus on the robustness of transcriptional networks in physiological, developmental and evolutionary time scales. We propose to go beyond mapping Network topologies to develop dynamical models of the behavior of transcriptional regulatory networks during physiological stress, during cellular and organismal development, and during the evolution of species. These goals will be achieved by bringing together experts in genomics, developmental biology, evolutionary biology, stress and physiology, network modeling, high performance and grid computing, chemistry, and physics. The overarching aim of the Centers research is to uncover the organizational principles that transcriptional regulatory networks share as they respond to physiological, development and evolutionary inputs and pressures. These principles are expected to reveal structure-function relationships in networks that lead to physiological and evolutionary robustness or, its complement, flexibility.